Biomedical subjects

A Korn

Publications and source records attributed to A Korn.

At least 73 records · Page 4Linked to original sources

PubMed1988

Effect of verapamil on basal and glucagon-dependent splanchnic glucose metabolism and insulin secretion in man.

To determine the effect of verapamil on basal and glucagon-induced changes in splanchnic glucose metabolism and insulin secretion, six healthy men were studied during a primed-continuous infusion of verapamil (2.5 micrograms/kg/min). After a basal period of 30 min, glucagon was infused at a rate of 12 ng/kg/min for an additional 60 min. Splanchnic exchange of glucose, lactate, alanine and beta-hydroxy-butyrate, as well as splanchnic C-peptide release, reflecting insulin production rate, were determined by means of the liver vein catheter technique. Intraindividual control trials without verapamil were performed. Basal and glucagon-stimulated arterial glucose and insulin concentrations as well as insulin production rate were not significantly altered by verapamil, which also had no influence on basal splanchnic glucose output or on the glucagon-induced initial (0-30 min) increment in splanchnic glucose output. However, the gradual decline in splanchnic glucose output was delayed at 30-60 min (verapamil: 55.85 +/- 6.31 control: 39.73 +/- 5.6 mmol/30 min; mmol/30 min, mean, s.e.m., p less than 0.02). Splanchnic lactate-alanine- and beta-hydroxy-butyrate exchange were also unchanged by verapamil. We conclude that verapamil attenuates glucagon's evanescent effect on splanchnic glucose output without interfering with the exchange of gluconeogenic precursors or beta-hydroxy-butyrate or insulin production rate.

Adult↗

PubMed1988

Tyramine pressor effect in man: studies with moclobemide, a novel, reversible monoamine oxidase inhibitor.

The pressor effect of tyramine (TYR) administered i.v. and orally was measured in healthy volunteers during treatment with different therapeutic doses of moclobemide, a new, reversible, preferential type A monoamine oxidase inhibitor. With moclobemide 3 X 100 mg/day the systolic blood pressure (SBP) increase produced by TYR administered i.v. was potentiated 2.4-fold and that in response to TYR p.o. in the fasting state was increased 4.1-fold, as determined from equieffective TYR doses before and during moclobemide treatment. Peak concentrations of free TYR in plasma after oral doses of TYR were increased 2.6-fold, and a 2.5-fold smaller plasma TYR concentration produced the same SBP rise as before moclobemide treatment. No SBP increase was observed at plasma TYR concentrations below 20 ng/ml or after p.o. TYR does smaller than 80 mg. The potentiation of the pressor effect of i.v. TYR by single moclobemide doses up to 300 mg had disappeared 24 hrs after moclobemide administration. Peak TYR plasma concentration and concomitant SBP increments were considerably smaller when TYR was administered with a meal than when administered as a bolus with tap water, 2.1 times higher oral TYR doses being required to achieve similar peak TYR plasma concentration as in the fasting condition. The pressor effect of TYR was further, but only slightly, increased during treatment with moclobemide 3 x 200 mg/day, however SBP rises were again significantly smaller when TYR was given together with a meal. In contrast, tranylcypromine produced a 20 to 40-fold potentiation of the pressor effect of oral TYR and this potentiation was only slightly smaller when TYR was given with a meal. In conclusion the potentiation by moclobemide of the pressor response to oral TYR corresponds roughly to a fourfold left shift of the TYR dose-pressor response curve and is about 10 times less marked than after tranylcypromine. In real life situations, the ingestion of TYR in amounts less than 100 mg is highly unlikely to produce a clinically relevant blood pressure elevation.

Adult↗

PubMed1987

[Right heart failure as a clinical sign of pulmonary artery sarcoma].

A 43 year-old female patient was admitted on account of severe dyspnoea of several months' duration and thrombocytopenia. The clinical symptomatology was compatible with pulmonary embolism, but no source of embolization was found and heparin therapy did not lead to clinical improvement. Angiography of the pulmonary artery revealed multiple filling defects. Symptoms improved after treatment with cortisone and so a malignant process was assumed. The patient died from right ventricular failure before the diagnosis could be established. At autopsy a sarcoma of the pulmonary artery, obviously originating from the pulmonary trunk was found. Thrombocytopenia most probably resulted from consumption of platelets by a mechanism corresponding to the Kasabach-Merritt syndrome. The difficulties in the diagnosis of pulmonary artery sarcomas are discussed and the 69 previously published cases are reviewed.

Adult↗

PubMed1987

Disposition kinetics of moclobemide, a monoamine oxidase-A enzyme inhibitor: single and multiple dosing in normal subjects.

The absorption and disposition kinetics of moclobemide (Ro 11-1163), a new reversible and preferential monoamine oxidase-A enzyme inhibitor, were examined in 12 normal male subjects. An intravenous infusion was administered before and after a 15-day multiple oral dosing regimen (100 mg t.i.d.). Plasma concentration-time data were obtained after each intravenous infusion, after the first oral dose, during two dosing intervals at steady state, and before the second daily dose on several days. The disposition values (percent coefficient of variation in parentheses) after the first and second intravenous infusions, respectively, were: clearance, 39.4 (15%) and 29.1 (12%) L/hr; elimination half-life, 1.60 (15%) and 2.00 (18%) hours; and volume of distribution at steady state, 84.3 (11%) and 80.7 (15%) L. The absolute oral bioavailability increased from 0.56 after the first oral dose to 0.86 and 0.90 after the first and second weeks of administration, respectively. The reduced metabolic, presumably hepatic, clearance may be the result of self-inhibition or metabolite inhibition of moclobemide clearance.

Administration, Oral↗

PubMed1987

Effect of calcium antagonists on basal and digitalis-dependent changes in splanchnic and systemic hemodynamics.

We investigated the effects of the calcium antagonists verapamil and tiapamil on basal splanchnic and systemic hemodynamics and digoxin-induced vasoconstriction in 16 healthy men, using the hepatic venous catheter technique, the thermodilution method, and systolic time intervals. After a baseline period, verapamil or tiapamil were given by a primed-constant infusion in six of 16 subjects each, and hemodynamic changes were determined. Thereafter digoxin (1 mg) was concomitantly infused and hemodynamic changes were observed over 105 minutes. Control trials with digoxin alone were performed in seven of 16 subjects. Four of 16 subjects received only placebo. Digoxin provoked an increase in systolic blood pressure and splanchnic vascular resistance. Estimated splanchnic blood flow, mean pulmonary artery pressure, and total electromechanical systole decreased. Verapamil did not change basal hemodynamic parameters. Tiapamil decreased diastolic blood pressure and systemic and splanchnic vascular resistance. Both drugs attenuated the vasoconstricting effect of digoxin on the splanchnic vascular bed. Results indicate that calcium antagonists might be beneficial in treatment of digitalis-induced splanchnic vasospasm.

Adult↗

PubMed1987

Relative bioavailability of ofloxacin tablets in comparison to oral solution.

Single oral doses of solution and tablet preparations of 300 mg ofloxacin were given to 13 healthy male volunteers in an open, randomized crossover study. Concentrations of the unchanged drug were monitored at various times in serum and urine, over 28 hours and 48 hours, respectively. Each dose was followed by a 1-week washout period. Drug concentrations were measured both by a specific high pressure liquid chromatography (HPLC) method and a microbiological assay. A linear distribution independent regression analysis for method comparisons was calculated and good agreement between the two methods was found. Medians of maximum serum concentrations (Cmax) of ofloxacin after oral solution and tablet form were 5.0 mg/l and 3.5 mg/l, respectively. The times to maximal serum concentration (tmax) were 0.5 hr and 1.0 hr, respectively. The lower Cmax and later tmax after the tablet form were both statistically (p less than 0.05) different when compared to the corresponding values after the oral solution. However, the areas under the serum concentration-time curves (AUC0-28), as also the urinary recoveries did not differ significantly, showing that only the speed of absorption, but not the bioavailability of the tablet is changed in comparison to the oral solution form. Long-lasting, clinically relevant urine concentrations of ofloxacin were observed after both forms until the last collecting fraction (36 to 48 hours after medication). General tolerability was good; no side-effects were reported.

Administration, Oral↗

PubMed1987

Effect of stress hormones on splanchnic substrate and insulin disposal after glucose ingestion in healthy humans.

To compare cortisol and epinephrine action on oral glucose tolerance, healthy humans were infused with either cortisol (0.1 mg X kg-1 X h-1), epinephrine (5.4 micrograms X kg-1 X h-1), or saline before and after a 75-g glucose load, thereby elevating the respective plasma hormone concentrations into the pathophysiologic range. In the basal state, epinephrine increased arterial concentrations of glucose, beta-hydroxybutyrate, and free fatty acids (FFA) as well as splanchnic output of glucose and beta-hydroxybutyrate and splanchnic FFA more than cortisol. Postprandially, C-peptide release and hyperinsulinemia were blunted by epinephrine initially and increased less thereafter than during cortisol infusion. The rise in arterial glucose after glucose ingestion as calculated by the area under the curve was more marked (P less than .01) after epinephrine [( 1.90 +/- 0.08 M) 150 min] and cortisol [( 1.41 +/- 0.05 M) 150 min] than in the control study [( 1.07 +/- 0.04 M) 150 min]. In parallel, the stress hormones induced an almost identical 24 and 31% rise in mean splanchnic glucose output versus control values (normal, 44.8 +/- 2.5; cortisol, 55.3 +/- 3.3; epinephrine, 58.9 +/- 6.9 g/150 min). The associated rise in arterial concentrations and splanchnic output of insulin above control values was considerably greater during cortisol but unchanged during epinephrine exposure. Epinephrine but not cortisol induced a rise versus the control study in splanchnic uptake of lactate and FFA, as well as in pyruvate output, whereas plasma beta-hydroxybutyrate and acetoacetate remained unchanged. The postprandial splanchnic glucose output-to-splanchnic C-peptide output ratio did not differ from normal during epinephrine but was reduced (P less than .01) during cortisol administration.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗

PubMed1987

Nifedipine antagonizes alpha-adrenoceptor mediated splanchnic and systemic vasoconstriction in man.

Aim of the study was to investigate whether nifedipine interacts with alpha1-mediated splanchnic and systemic vasoconstriction in man. The effects of nifedipine on basal and phenylephrine (PE)-induced hemodynamic changes were studied in 6 normotensive men, using the hepatic venous catheter technique (indocyanine-green) and the thermodilution method. After a baseline period, nifedipine was given by constant infusion (0.5 microgram/kg/min) and, after equilibration, PE was infused at a constant rate in a dose sequence of 1, 2, 3, and 4 micrograms/kg/min, until the systolic blood pressure was raised by 30 mmHg. Control trials without nifedipine (saline) were also performed in each subject. At basal conditions nifedipine decreased systemic blood pressure and total systemic vascular resistance (TSVR) as well as total pulmonary vascular resistance (TPVR), and increased cardiac output (CO). PE provoked a dose-dependent increase in systemic blood pressure, TSVR and TPVR, and decreased CO. These PE-effects were clearly attenuated by nifedipine. In the splanchnic vascular bed nifedipine increased estimated splanchnic blood flow (ESBF) and decreased splanchnic vascular resistance (SVR) at basal conditions. The PE-induced decrease in ESBF and increase in SVR were inhibited or attenuated (depending on PE-dosage) by nifedipine. We conclude that nifedipine counteracts alpha1-adrenoceptor mediated systemic and splanchnic vasoconstriction and therefore, might also be useful in the treatment of intestinal vasospasm.

Adult↗

PubMed1987

Diltiazem counteracts digitalis-dependent splanchnic vasoconstriction in man.

We investigated the vasodilating effect of diltiazem on basal as well as digoxin-dependent splanchnic and systemic hemodynamics in 12 normotensive men, using the hepatic venous catheter technique, the thermodilution method and systolic time intervals. After baseline measurements, diltiazem was administered by a primed-constant infusion (2.5 micrograms/kg/min) in 6 out of 12 subjects. Following an equilibration period of diltiazem infusion, 1 mg digoxin was infused concomitantly over 15 min and hemodynamic changes were determined over 105 min. Control trials with digoxin and concomitant saline infusion were also performed in 7 out of 12 subjects. Diltiazem medication alone lowered only systolic blood pressure without affecting splanchnic hemodynamics. Digoxin without comedication provoked an increase in systolic blood pressure, a decrease in heart rate, mean pulmonary artery pressure and total electromechanical systole (positive inotropic effect), and significantly reduced splanchnic blood flow and increased splanchnic vascular resistance. During concomitant diltiazem infusion, digoxin did not alter splanchnic hemodynamics while the shortening of total electromechanical systole remained unchanged. We conclude, that diltiazem attenuates digoxin-induced splanchnic vasoconstriction and therefore, might be useful in the treatment of digitalis-dependent splanchnic vascular insufficiency.

Adult↗

PubMed1987

Comparative effects of verapamil, tiapamil, diltiazem and nifedipine on systemic and splanchnic hemodynamics in man.

The vasodilating effects of verapamil, tiapamil, diltiazem and nifedipine on splanchnic and systemic circulation have been investigated in 18 male normotensive subjects by means of the hepatic venous catheter technique, the thermodilution method and systolic time intervals. After a baseline period, calcium antagonists were administered by a primed-constant infusion. Hemodynamic changes were assessed after an adequate equilibration period. Verapamil did not change splanchnic or systemic hemodynamics. Tiapamil decreased diastolic blood pressure and systemic vascular resistance as well as splanchnic vascular resistance, and increased cardiac output. Diltiazem lowered only systolic blood pressure without effecting splanchnic circulation. The most pronounced vasodilating effect was seen with nifedipine. It significantly reduced systolic and diastolic blood pressure, systemic vascular resistance and also splanchnic vascular resistance. Our present data seem to indicate that nifedipine and tiapamil are more effective vasodilators, especially in the splanchnic vascular bed, as compared to verapamil and diltiazem. We conclude that these two calcium antagonists might be useful in the treatment of intestinal (splanchnic) vasoconstriction.

Adult↗

PubMed1986

Moclobemide, a new reversible MAO inhibitor--interaction with tyramine and tricyclic antidepressants in healthy volunteers and depressive patients.

Moclobemide is a new, short-acting, reversible MAOI, preferentially affecting type A MAO. We have studied the interaction of moclobemide with tyramine and tricyclic antidepressants in healthy volunteers and depressive patients. Neither tyramine capsules (50 mg) nor cheese and wine meals (65 mg tyramine) produced a significant change in blood pressure and heart rate after single or repeated doses of moclobemide in volunteers. In contrast, after 1 weeks' treatment with tranylcypromine pressure response to cheese and wine meals was severe. Blood pressure sensitivity to IV tyramine was slightly increased (1.5-2 fold; P less than 0.05 versus predrug) during moclobemide treatment in patients and volunteers. This increase was neutralised by concomitant administration of desipramine in volunteers. Amitriptyline was well tolerated when given to patients after or together with moclobemide. In conclusion, moclobemide appears relatively safe with respect to tyramine sensitivity and interaction with tricyclics.

Adult↗

PubMed1986

Effect of diclofensine, a novel antidepressant, on peripheral adrenergic function.

Diclofensine is a novel antidepressant with equipotent inhibitive effects on the neuronal uptake of norepinephrine (NE), serotonin, and dopamine. It is devoid of monoamine-releasing or monoaminoxidase-inhibiting properties. The action of diclofensine on peripheral neuronal adrenergic function was studied through tests of the blood pressure response to NE, tyramine, and phenylephrine (PE). The blood pressure response to NE was enhanced and that to tyramine was decreased by diclofensine, as a result of its inhibitive action on peripheral neuronal amine uptake. PE sensitivity was also enhanced by diclofensine as well as after a single dose of desmethylimipramine (DMI). In contrast to the common opinion that PE does not interact with the neuronal uptake mechanism, the increase in PE-induced blood pressure response after diclofensine and DMI suggests that PE, a nonbiogenic amine, does indeed enter into the peripheral adrenergic neuron. This neuronal uptake may probably be unmasked only by powerful NE uptake inhibitors such as DMI or diclofensine.

Administration, Oral↗

PubMed1986

In vivo clearance of antibody-sensitized human drug carrier erythrocytes.

Antibody coating of resealed drug carrier erythrocytes may be useful for drug targeting to the reticuloendothelial system. We have investigated the survival in the circulation of anti-Rh antibody (IgG anti-D)-coated autologous erythrocytes loaded with gentamicin by hypoosmotic dialysis. Five subjects were injected with 15.2 +/- 0.4 ml and five additional subjects with 62.8 +/- 1.5 ml carrier cells. Survival of the cells was monitored by intraerythrocytic gentamicin concentration in blood. In the first subject group initial t1/2 was 0.21 +/- 0.06 hours and terminal t1/2 was 1.71 +/- 0.36 hours. In the second group initial t1/2 was 0.59 +/- 0.21 hours followed by a slow phase with a t1/2 of 89 +/- 28 hours. Results indicate that rapid drug delivery to the reticuloendothelial system by antibody-sensitized carrier erythrocytes is possible, but small volumes of erythrocytes seem more efficient.

Adult↗

PubMed1986

Survival of gentamicin-loaded carrier erythrocytes in healthy human volunteers.

Resealed erythrocytes are potential slow release carriers for drugs and enzymes. We have investigated carrier erythrocyte survival in human volunteers using gentamicin (G) as encapsulated cell marker; G was readily incorporated into red cells by hypo-osmotic dialysis (87% efficiency of incorporation) and did not exit from carrier cells in vitro. Six healthy young volunteers were injected with 59 +/- 7 ml carrier erythrocytes containing 56 +/- 13 mg G. G levels were measured in plasma and haemolysed whole blood by RIA. After an initial phase of cell loss (up to 4.5 h post-injection) the carrier erythrocytes survived in circulation with a half-life of 22 days, as was indicated by intracellular G concentration. G levels were detectable in plasma during the first 90 min after injection. This indicates haemolysis of some carrier cells. In conclusion, carrier erythrocytes appear to circulate longer than any other drug carrier under investigation and may well serve as innocuous slow release system.

Adult↗

PubMed1986

The effect of food on the pharmacokinetics of ofloxacin.

After oral administration of a single dose of ofloxacin (300 mg), with and without a standard breakfast, to 12 healthy male volunteers in an open, randomized crossover study, concentrations of the unchanged drug were estimated at various times in serum and urine, over 28 hours and 48 hours, respectively. Each dose was followed by a wash-out period of 1 week. Ofloxacin concentrations were determined using high pressure liquid chromatography (HPLC): parallel determinations using a microbiological assay were in close agreement. Maximum serum concentrations (Cmax) of ofloxacin, after fasting and with breakfast, respectively, were 3.7 and 3.1 micrograms/ml (HPLC, median values). The corresponding areas under the serum concentration-time curves (AUC0-28) were 29.9 and 24.5 micrograms/ml. The lower values of Cmax and AUC0-28 found after food intake were statistically significant (p less than 0.05) but not clinically relevant when compared to the fasting values. Time to reach Cmax and terminal elimination half-life (t1/2 beta) were not significantly affected by food intake: t1/2 beta was calculated as 5.3 and 5.9 hours (HPLC, median values), fasting and with breakfast, respectively. Urinary recovery (after 48 hours: 72% and 74%, respectively) was also not significantly affected by food intake, and urinary concentrations of ofloxacin remained far above 1 microgram/ml, i.e. above the minimum inhibitory concentration (MIC90) for most bacterial strains, for at least 48 hours after drug administration. General tolerability was good; no side-effects were reported.

Adult↗

PubMed1986

Improved methods for venous access: the Port-A-Cath, a totally implanted catheter system.

We prospectively evaluated the performance and rate of long-term complications with the Port-A-Cath (PAC), a totally implanted vascular access system. Two catheter styles were evaluated, a small-bore (SB) catheter (0.51-mm diameter) and a large-bore (LB) catheter (1.02-mm diameter), in conjunction with the use of a strict catheter care protocol. The PAC performed well, and with both SB and LB systems, no significant extravasation, skin necrosis, hematoma, septum damage or leakage, or subcutaneous portal infections occurred after 7,240 days of implantation and 1,435 days of use. Complications with the PAC system consisted of catheter occlusion (seven patients, 21.5%) and one instance of possible catheter infection (3.1%). Occlusions were limited to patients implanted with the SB catheter (seven of 16, 43.8%), and five of the seven (71.4%) occurred in patients receiving continuous infusion chemotherapy and/or total parenteral nutrition. Patency of the PAC system was maintained using a regular flushing schedule once every 30 days, a significant advantage compared with the daily maintenance schedule required with externally placed venous catheters. The results of this study suggest that the PAC system can provide a safe and reliable method for venous access in patients requiring intermittent or prolonged intravenous therapy.

Adult↗

PubMed1986

A drug interaction study of ceftriaxone and frusemide in healthy volunteers.

Ceftriaxone, a recently developed cephalosporin significantly reduced the diuretic activity of frusemide in rats. For this reason and because an interaction of unknown mechanism is well established between frusemide and some cephalosporins, we studied the interference of ceftriaxone with the diuretic effect of frusemide in healthy volunteers. Twelve subjects received frusemide (40 mg p.o.) or placebo in combination with ceftriaxone (2 g i.v.) or saline on 4 different days (cross-over, randomized, single-blind study). Urine was collected in small portions during 24 hours after medication and analyzed for volume, osmolality, Na+, K+, Cl- and creatinine concentration. Ceftriaxone had neither an effect on basal urinary output and electrolyte excretion nor on the specific diuretic action of frusemide.

Adult↗

PubMed1985

[Open study on the effect and side effects of indoramin, used at the 2d and 3d therapeutic step in essential hypertension].

An open study was undertaken to investigate the efficacy and adverse effects of indoramin in 33 patients with essential hypertension whose blood pressure was uncontrolled (diastolic blood pressure 96 to 115 mm Hg) despite previous treatment with one or two antihypertensive drugs. Indoramin was added to the existing antihypertensive therapy and the dose titrated to a maximum of 150 mg/day or until blood pressure control was achieved (diastolic blood pressure less than 90 mm Hg or a reduction in diastolic blood pressure of 15 mm Hg). Patients were then followed up for a further 4 weeks. Indoramin significantly reduced mean standing systolic and diastolic blood pressure from 167/113 +/- 19.8/7.2 (SD) mm Hg to 150.3/101.1 +/- 23.4/8.9 (SD) mm Hg after 10 weeks and mean supine systolic and diastolic blood pressure from 169.8/110.8 +/- 16.4/5.6 (SD) mm Hg to 154.2/102.1 +/- 23.8/12 (SD) mm Hg after 10 weeks. Blood pressure was controlled in 21 of the 33 patients (63.6%) studied. Indoramin caused a small but significant fall in pulse rate of 3.9 beats per minute, in the supine position, after 4 weeks therapy. 10 patients experienced adverse effects, the most common being dizziness and headache (3 patients each), and lightheadedness/fainting on standing (2 patients). No patient experienced sedation. Only 1 patient was withdrawn from the trial because of adverse effects (fainting on standing). Biochemical and haematological investigations carried out pretreatment and during treatment showed no abnormalities related to indoramin treatment.

Adult↗